PB1871: HIGH RATES OF INFECTION AND RELATED MORALITY FROM VENETOCLAX THERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKAEMIA: A SINGLE CENTRE RETROSPECTIVE STUDY
Authors: Durga Chandran, Nicholas Viiala, Anne-Marie Watson, Lindsay Dunlop, Penelope Motum, Nagendraprasad Sungala, Heather Range, Bartlomiej Getta
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Venetoclax is a BCL-2 inhibitor approved for use in combination with Azacitadine or low dose Cytarabine (LDAC) in the front-line treatment of acute myeloid leukaemia (AML) in those aged over 75 or unfit for intensive induction. There is limited data on this combination in the treatment of refractory/relapsed (R/R) AML, specifically its infective complications and related mortality. Aims: To quantify the incidence and types of infective complications, disease response and overall survival in patients receiving Venetoclax therapy for R/R AML. Methods: This was a single centre retrospective study investigating infective complications in 18 patients with R/R AML who received Venetoclax based therapy between 2018-2021. Data was collated from electronic medical records. Venetoclax was sourced through compassionate access limited to subjects with R/R AML and no alterative therapy options. Subjects had to be ECOG 2 or less to be eligible. Incidence of bacterial, fungal and viral infections and febrile neutropenia was recorded for cycle 1 and separately for additional cycles. Bacterial infections were defined by positive culture, viral infections by nucleic acid detection and invasive fungal infections (IFI) were defined as proven or probable using standard criteria. All subjects received anti-viral prophylaxis with valaciclovir and anti-fungal prophylaxis with Posaconazole, Voriconazole or Amphotericin. Bacterial and Pneumocystis Pneumonia (PJP) prophylaxis was not routinely administered. The study was approved by the local IRB (ETH00747). Results: Demographic data is presented in Table 1. 11 patients (61%) suffered infection in cycle 1 of Venetoclax, with 10 having febrile neutropenia (56%). This included 2 cases of confirmed PJP on PCR, 5 bacteraemias, 2 aspergillus IFIs and 1 rhinovirus infection. The infectious mortality rate in the first cycle was 33%. 4 of the 7 patients (57%) who received more than 1 cycle of treatment died within 6 months, all from sepsis. Overall response rate (ORR) was 29% among 14 patients who had documented responses. The median overall survival (OS) from treatment commencement was 70 days (95% CI 5-150 days). 3 (17%) survived more than 12 months, 3 underwent allograft, 1 remains alive 3 years post allograft and 1 was lost to follow up. Table 1. Demographics, Disease and Treatment CharacteristicsSummary/Conclusion: This study show high rates of infection and related mortality in patients receiving Venetoclax therapy for R/R AML from neutropenic sepsis. Of note, there were 2 cases of PJP pneumonia and 2 IFIs suggesting anti-fungal and PJP prophylaxis should be strongly considered when using Venetoclax in R/R AML. The response rates after cycle 1 were modest with ORR 29% and median OS of 70 days. Keywords: relapsed/refractory, Venetoclax, Infection, AML